Chiroptical spectroscopic methods will be utilized to probe molecular conformation in solution. The results of experimental circular dichroism studies will be compared with the results of theoretical calculations. The calculations will be carried out by means of a theoretical formalism which utilizes spectroscopic data determined from studies of model compounds to calculate the optical properties of macromolecules. The procedure will first be tested with small, conformationally hindered molecules which contain the chromophoric group(s) of interest. The technique is then applied to much more complex macromolecular systems which contain the same chromorphoric groups. The primary goal will be to develop techniques for probing the secondary and tertiary structure of proteins by means of the chiroptical properties of the amino acid side chain chromophores. Attempts will be made to compare the structure of proteins in solution with structures determined in the solid state by means of X-ray diffraction studies of crystals. Studies of minor conformational changes which occur upon the binding of inhibitors and/or substrates to enzymes will also be carried out.